1. Field of the Invention
A fiber optic based dynamic light scattering apparatus is disclosed for in-vivo characterization of the concentration and size of various protein macromolecules in the anterior segment of the eye, which includes the crystalline lens, the aqueous humor and the cornea. A lens-less fiber optic probe comprising two optical fibers may be fixed onto an aplanation tanometer mount, which is a universal accessory to any commercial slit lamp microscope. A monomode optical fiber guides light from a semiconductor laser source to a point inside the eye lens, and a second optical fiber, positioned in close proximity, is used for coherent detection of the scattered light in the backward direction. The free end of the receiving optical fiber is connected to a photodetector, typically a photomultiplier. In this manner, light is detected and converted into a pulse position modulated electrical waveform, which is processed by a digital correlator to yield the first order electric field autocorrelation of the scattered laser light. Subsequent inversion of the data yields a distribution of diffusion coefficients, which can be scaled to give a distribution of particle size or molecular weight. The ability to track small changes in concentration and size are vital for the early detection and prevention of ocular disorders, such as cataractogenesis.
2. Brief Description of the Prior Art
Cataract surgery is inevitable in many humans because of the changes caused to the transparency of the eye due to aging. Other known factors such as high blood sugar levels and long exposure to ultra violet light can accelerate this process. Current state-of-art systems, which include visual inspection through a slit lamp microscope or analysis of a photographic plate, lack the sensitivity to detect small molecular changes in the ocular tissue. Early detection of changes in relative concentration and size of the different protein species will permit development of preventive therapy, and possible reversal of cataractogenesis. A reliable apparatus for non-invasive, rapid, quantitative and causing the least trauma to the patient, has been long sought goal for the study of cataractogenesis and other ocular disorders.
In the last three decades, following the invention of the laser, light scattering (LLS) has become an indispensable, non-invasive, and extremely sensitive technique for routine characterization of molecular changes in physiological, chemical, polymer and colloidal systems. A conventional light scattering apparatus requires illumination of the sample by a coherent source, detection of the weak scattered light at some specified scattering angle, processing of the data and inversion to yield the required information of size and shape. Until recently, conventional LLS systems, because of their large size and sensitivity to vibrations, were confined to a research laboratory. However, in the last five years, significant advances have been made in the miniaturization of these systems by utilizing fiber optics, semiconductor laser sources and detectors. Data acquisition and analysis have also been dramatically improved due to rapid technological advances in the microelectronics industry.
LLS, in particular dynamic light scattering (DLS) or quasielastic light scattering, or intensity fluctuation spectroscopy, or photon correlation spectroscopy, has been successfully used for the characterization of protein macromolecules in excised eye lenses, however, a clinical apparatus in still not available. Benedek [U.S. Pat. No. 4,957,113] and Benedek and Magnante [U.S. Pat. No. 4,993,827] have disclosed an apparatus and a method for detection of ophthalmic diseases, respectively. Their apparatus comprises a conventional light scattering system, with all its inherent alignment and stability problems. A person skilled in the art usually requires several hours to align a conventional DLS apparatus. Analysis techniques described in the latter patent have been employed by researchers for the last two decades and have been commercially available for many years.
Other apparatus pertaining to the detection of ophthalmic diseases are not based on dynamic light scattering, and therefore do not provide information on the molecular changes of the protein macromolecules. U.S Pat. Nos. 4,776,687 and 4,854,693 disclose such apparatus.